Fitzgerald John P, Chou Shyan-Yih, Franco Israel, Mooppan Unni M, Kim Hong, Saini Rajiv, Gulmi Frederick A
Department of Urology, Brookdale University Hospital and Medical Center, Brooklyn, New York 11212, USA.
J Urol. 2009 Oct;182(4 Suppl):1860-8. doi: 10.1016/j.juro.2009.04.086. Epub 2009 Aug 18.
Tubulointerstitial fibrosis, the histological feature of chronic obstructive nephropathy, is delineated in complete unilateral ureteral obstruction models. Histological changes during chronic partial ureteral obstruction are not well studied. We describe changes in a rat model of partial ureteral obstruction. We examined the effects of atorvastatin on histological alterations, fibrosis and function in this model.
All rats underwent right nephrectomy. To create partial ureteral obstruction the left ureter was incorporated into the psoas muscle, which was split and reapproximated. Excretory urogram, histology, Western blot of alpha-smooth muscle actin and renal clearance were examined in rats with sham, 14-day or 30-day partial ureteral obstruction. Obstructed rats received a regular or a diet supplemented with 50 mg/kg body weight atorvastatin per day.
At 14 days of partial ureteral obstruction pyelogram showed hydronephrosis, which was more pronounced on obstruction day 30. Histological studies on obstruction days 14 and 30 revealed tubulointerstitial fibrosis in the medulla and cortex. Atorvastatin significantly decreased tubulointerstitial fibrosis seen in alpha-smooth muscle actin expression. On obstruction day 14 or 30 the glomerular filtration rate in rats on a regular diet was significantly lower than in sham PUO rats or rats on atorvastatin.
This model of partial ureteral obstruction enables chronic studies of morphological and histological changes of the obstructed kidney. It showed progressive fibrosis and decreased filtration function. Atorvastatin ameliorated fibrosis and helped preserve kidney filtration function.
在完全性单侧输尿管梗阻模型中描述肾小管间质纤维化，这是慢性梗阻性肾病的组织学特征。慢性部分性输尿管梗阻期间的组织学变化尚未得到充分研究。我们描述了部分性输尿管梗阻大鼠模型中的变化。我们研究了阿托伐他汀对该模型中组织学改变、纤维化和功能的影响。
所有大鼠均接受右肾切除术。为造成部分性输尿管梗阻，将左输尿管纳入腰大肌，劈开腰大肌并重新缝合。对接受假手术、部分性输尿管梗阻14天或30天的大鼠进行排泄性尿路造影、组织学检查、α-平滑肌肌动蛋白的蛋白质印迹分析以及肾脏清除率检测。梗阻大鼠接受常规饮食或每天补充50mg/kg体重阿托伐他汀的饮食。
部分性输尿管梗阻14天时肾盂造影显示肾盂积水，在梗阻第30天时更为明显。梗阻第14天和30天的组织学研究显示髓质和皮质出现肾小管间质纤维化。阿托伐他汀显著降低了α-平滑肌肌动蛋白表达中所见的肾小管间质纤维化。在梗阻第14天或30天，常规饮食大鼠的肾小球滤过率显著低于假手术部分性输尿管梗阻大鼠或阿托伐他汀治疗大鼠。
该部分性输尿管梗阻模型能够对梗阻肾脏的形态学和组织学变化进行长期研究。它显示出进行性纤维化和滤过功能下降。阿托伐他汀改善了纤维化并有助于保留肾脏滤过功能。
